1. Field of the invention
The present invention relates to the use of Carnitine for enhancing or achieving training-induced bradycardia in a human or in a mammal, preferably in a horse. It further relates to the use of Carnitine for strenghtening the equine heart. Another object of the invention is the use of Carnitine for manufacturing a pharmaceutical or nutritional preparation destined to enhance training induced-bradycardia in a human upon physical training.
2. Description of Related Art
In a number of mammalian species, especially in man, physical exercise aiming at increasing physical fitness leads to improved cardiac performance. Prolonged exercise causes an increase in heart size and stroke volume. As a result of these adaptations, the trained and strengthened heart contracts less often at the same work load while expelling the same amount of oxygenated blood which is conveyed to the tissues as before the onset of training. The cardiac minute volume (MV) which is the product of stroke volume (SV) and pumping rate (heart rate, HR) is usually unchanged at the same level of physical exercise before and after a training period. At rest and in the absence of physical stress the HR is markedly decreased after a period of physical training while the SV is concomitantly increased, thus keeping the MV essentially the same: SVxc3x97HR=MV. The lowering of HR at rest and during exercise is called training-induced bradycardia. It is caused by an enlargement of the heart upon training, said enlargement being due to an increase in volume of individual heart muscle fibres. Concomitantly, the filling volume of the heart and the stroke volume are increased (Scheuer, J. et al., Cardiovascular adaptations to physical training. Ann. Rev. Physiol. 1977, 39: 221).
A training-induced bradycardia is accompanied by an enhanced resistance to fatigue and better performance of the heart under maximal physical strain as compared to the untrained heart. This phenomenon is known since the early nineteen thirties and has since been confirmed in numerous studies. Even under graded, moderate physical stress, the heart of trained individuals will beat slower than that of the untrained individual (Schaible, T. et al., Effects of physical training by running or swimming on ventricular performance of rat hearts. J. Appl. Physiol. 1979, 46:854; Pechar, G. et al., Specificity of cardiorespiratory adaptation to bicycle and treadmill training. J. appl. Physiol 1974, 36:753). The HR reducing effect has been demonstrated for man and animals, being most pronounced during the first two to three weeks of training. Only a moderate further reduction is achieved thereafter which will almost cease after three to four months of continuous training. At this time the training-induced bradycardia can be regarded as maximal (Tipton, C., Training an bradycardia in rats. Am. J. Physiol. 1965, 209:1089; Scheuer J. et al ., Cardiovascular adaptations to physical training. Ann. Rev. Physiol. 1977, 39:221).
Whilst being most pronounced in man, training-induced bradycardia is not unique to man. The phenomenon has repeatedly been described for dogs and rats (Wyatt, H. et al., Influences of physical training on the heart of dogs. Circ. Res. 1974, 35: 883; Tipton, C., Training and bradycardia in rats, Am. J. Physiol. 1965, 209:1089; Codini, M. et al., Cardiac responses to moderate training in rats, J. Appl. Physiol. 1977, 42:262).
Quite in contrast, up to now, training-induced bradycardia has been literally unknown in the case of horses. Though this would be a much desired effect for racing horses (trotters), it has been futilely sought in a number of research projects (Bayly, W. et al., Am. J. Vet.
Res. 1983, 44:544; Skarda, R. et al., Am. J. Vet. Res. 1976, 37:1485; Fregin, G. and Thomas D. P., in: Equine Exercise Physiology. Eds. Snow, D. H. et al., Burlington Press Ltd./Cambridge 1983, 76; Persson, S. G. B. et al., in: Equine Exercise Physiology. Eds. Snow, D. H. et al., Burlington Press Ltd./Cambridge 1983, 458; Rose, R. J. et al., 1983, Vet. Rec. 113:612; Miller, P. A: and Lawrence L. M., in: J., Equine Exercise Physiology II, Eds. Gillespie, J. R. and Robinson, N. E., ICEEP Publications, San Diego, 1987, 476). This is likely due to the fact that horses have been evolutionary optimized for physical performance and endurance exercise upon running. In comparison to other animal species, the parasympathetic input into the equine heart is likely to be higher. This higher autonomic nervous input appears partly be responsible for the relatively low heart rate of horses at rest and during moderate intensities of exercise. An increased parasympathetic control of the equine heart is probably due to genetic factors, programming the organ to a relatively high standard of physical performance.
It is an object of the present invention to achieve or enhance a training-induced adaptation effect of the heart of a human or of a mammal, in particular of the equine heart, leading to increased endurance and improved performance. This object is achieved by administering carnitine to a human or to a mammal concomitantly to physical training.